Venclexta (venetoclax)

Herein, guided by the structural features of Sorafenib, the selective Bcl-2 inhibitor Venetoclax, and the selective Mcl-1 inhibitor AZD5991, we designed and synthesized a series of novel Sophocarpine-derived analogues bearing a pyridylethyl moiety via a molecular-hybridization strategy. In parallel, a 3D-QSAR (CoMFA) model was constructed to rationalize the structure-activity relationship and to inform further lead optimization. Collectively, these findings identify S6 as a promising Sophocarpine derivative with a putative dual Bcl-2/Mcl-1 targeting profile, with significant anti-HCC activity and potential for preclinical development.

P2, N=28, Recruiting, Seoul National University Hospital | Not yet recruiting --> Recruiting

P1, N=18, Recruiting, Canadian Cancer Trials Group | Trial completion date: Jul 2026 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P1, N=5, Completed, Dana-Farber Cancer Institute | Trial completion date: Feb 2026 --> Apr 2025 | Active, not recruiting --> Completed

The DNA hypomethylating agents (HMAs) 5-azacitidine and decitabine are the backbone of disease modifying therapy in myelodysplastic syndromes (MDS). We show that pyrimethamine, an FDA-approved antifolate, induces apoptosis across leukemic models, synergizes with venetoclax, and restores sensitivity in HMA- and venetoclax-resistant leukemia. Pyrimethamine promotes differentiation of stem and progenitor cells in primary MDS samples and in combination with venetoclax directly inhibits pyrimidine synthesis, revealing a clinically actionable strategy to overcome a key mechanism of therapeutic resistance.

Successful fixed-duration regimens in CLL should achieve deep remission (i.e., undetectable minimal residual disease), sustain long-term progression-free survival, decrease the burden of treatment-related adverse events, and allow for re-treatment with minimal risk of drug resistance. Although fixed-duration treatment represents a positive step forward for most patients with CLL/SLL, the currently approved regimens often fall short in patients at high risk of progression. Continued research and development of next-generation drugs is essential to enhance efficacy and safety, ultimately improving outcomes in all patients with CLL/SLL.

μPharma provides rapid (4-h assay), accurate, and automated prediction of drug sensitivity at single-cell resolution using minimal clinical samples, potentially enabling same-day precision oncology decision-making.

P=N/A, N=80, Not yet recruiting, Mianyang Central Hospital; Mianyang Central Hospital

P=N/A, N=52, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.; Institute of Hematolog

P=N/A, N=111, Completed, The first affiliated hospital, Zhejiang University School of Medicine; The first affiliated hospital, Zhejiang University School of Medicine

P=N/A, N=87, Not yet recruiting, Nanfang Hospital, Southern Medical University; Nanfang Hospital, Southern Medical University

P=N/A, N=34, Not yet recruiting, The Second Affiliated Hospital of Guangxi Medical University; The Second Affiliated Hospital of Guangxi Medical University